Franz cell is the commonly used test apparatus for studying of the transfer of a substance through a membrane. The Franz cell is in the form of a container with an upper half separated from a lower half by a membrane. In the upper compartment there placed a donor substance. The lower compartment is completely filled with a receptor media. The concentration of the testing substance in receptor solution is determined to study the diffusion rate of testing substance at a given time.
It is desired in clinical therapy to instantly understand the drug absorption from transdermal therapeutic preparation in human body when transdermal therapeutic preparation, such as nitroglycerin tape, ISDN tape, indomethacin gel, prednisolone ointment and so on, are applied. However, it is difficult to determine prolonged changes of drug diffusion rate just using said Franz diffusion cell.
In order to determine the permeation situation of the testing substance, the receptor solution have to be sampled at a given time. Therefore, a diffusion cell which is known as the Franz cell as shown in FIG. 1 was developed. FIG. 15 is the cross-sectional view of one of the examples of the diffusion cells developed.
100 is a cylindrical container defined by a flange on its top end. 200 is an upper container in shape of cylinder and fixed by a flange on its lower end. The container 100 is surrounded by a jacket 101 which has an inlet 102 and an outlet 103 integrally connected to the lower and upper wall of the jacket 101 respectively to supply and discharge of temperature-keeping liquid. Besides, a refilling port 104 for receptor media supply is connected to the lower wall of container 100. Connected to the middle wall of the container 100 is a branch shaped sample port 105 which has an internal sample tube 300 reaching at the near center of container 100 for sample-taking.
Using said diffusion cell to determine the transfer of the testing substance at any time, a stirrer 400 is firstly placed into the container 100. A membrane 500 is clamped between the flanges of container 100 and upper container 200. Then, the receptor media is supplied through the refilling port 104 to completely filling up container 100. Stirrer 400 is operated to cause the receptor liquid to be homogeneous.
Temperature-keeping liquid is to be supplied through the inlet 102 into jacket 101. A testing media is supplied into upper container 200 and in contact with membrane 500. At predetermined time interval, a known quantity of the receptor solution with permeated testing substance is removed through the sample tube 300 to determine the concentration of testing substance and additional quantity of fresh receptor media is supplied through refilling port 104 afterwards. (See references cited)
[Patent 1] U.S. Pat. No. 5,198,109
Although said diffusion cell can be used to determine the permeation of testing substance at any time, it is desirable to have the receptor solution maintained at a specifically known temperature level for 1 or several days when the permeation of testing substance in transdermal formulation to human body is studied. The way to achieve this is by supplying the liquid being at a pre-determined temperature through the inlet 102 to cause the circulation within the jacket 101 during the time. However, it is difficult to have the receptor liquid maintained at a specifically known temperature level for 1 or several days by this way.
Said diffusion cell may have to be immersed in a thermostatic water bath to finish the determination when there is no jacket 101 existed, resulting in difficult temperature control due to the water evaporation in water bath over a long time. In addition, volume of 3 to 10 ml of container 100 in said diffusion cell makes it difficult to keep the receptor liquid at a stable temperature over a long time.